The availability of structurally well-defined synthetic antigens permitted the elucidation of many aspects of the molecular and cellular basis of immunological phenomena. The present proposal is devoted mainly to problems of paramount importance for a better grasp of immunological phenomena, genetic control of immune response, the nature of immune response, the nature of immune response gene products, cell to cell cooperation, mechanisms involved in B cell triggering, and autoimmunity. Significant progress in elucidating the mechanisms responsible for generating genetic variations in the immune system was made by studying the genetic control of responses to synthetic antigens. The use of ordered peptides of known sequences opens the way for studies on a higher level of sophistication and thus for a better understanding of the molecular nature of genetic defects. The development of antigen specific T cell factors permits us to test directly the role of T and B cells in genetically regulated immune responses and the mechanism of cell to cell cooperation. The elucidation of the properties and molecular parameters of the antigen specific T cell factors is of great importance since their specificity and the fact that they are I region gene products strongly suggest that they represent the T cell recognition system. The objectives of the proposed research are: to continue to analyse the genetic control of immune response at the molecular and cellular levels, using synthetic polypeptides including ordered peptides as well as T independent immunogens, to elucidate the mechanism(s) by which immune genes are operating, to study the nature of immune response gene products and to establish the role of antigenic structure in cell to cell cooperation. We have also been interested in genetic regulation and cellular basis of the immune response to collagen and nucleic acids which are involved in some autoimmune diseases and in the nature of x-linked immune response genes which control responsiveness to nucleic acids. BIBLIOGRAPHIC REFERENCE: M. Sela and L. Mozes. Varied effects of polyadenylic-polyuridylic acid on immune responses. Biochemie 58, 173 (1976).